Immunomodulation induced by Ascaris suum extract in mice: effect of anti-interleukin-4 and anti-interleukin-10 antibodies.
Simultaneous immunization of mice with an Ascaris suum extract (Asc) and ovalbumin (OA) markedly affects the immune response to OA. The role of interleukin (IL)-4 and IL-10 induced by Asc immunization on the modulation of antigen-specific and mitogen-induced responses was investigated following single or combined cytokine-specific monoclonal antibody (MoAb) treatment of mice before immunization with OA + Asc. Immediate hypersensitivity reactions to aggregated OA and OA-specific immunoglobulin (Ig)G2a antibody production were completely restored only when both IL-4 and IL-10 were neutralized. These findings were associated with enhanced interferon (IFN)-gamma secretion by OA-stimulated lymph node (LN) cells. In addition, the Asc-specific cytokine response in anti-IL-4 plus anti-IL-10 MoAb treated mice was shifted towards a Th1 phenotype, with an increase in IFN-gamma and IL-2 levels and a decrease in IL-4, but not in IL-10, levels. Consequently, Asc-specific IgG2a antibody production increased, whereas IgE titres diminished in these animals. These results indicate that IL-4 and IL-10 act together in the Asc-induced mechanism of antigen-specific pansuppression. In contrast, modulation of Concanavalin A (Con A)-induced cytokine responses in Asc-immunized mice appears to be essentially mediated by an IL-4-dependent mechanism, since the neutralization of just IL-4 (and not of IL-10), either in vivo or in vitro, changed the cytokine profile from a Th2 towards a Th1 type. However, OA and Asc-specific cell responses were not modified by either anti-IL-4 or by anti-IL-4 + anti-IL-10 MoAbs in vitro treatments, suggesting that the induction of a Th2 response to Asc components concomitant to OA immunization has a strong suppressive effect on the priming stage of OA-specific Th1 type response.
Macedo
M S
MS
Department of Immunology, University of São Paulo, Brazil.
Faquim-Mauro
E
E
Ferreira
A P
AP
Abrahamsohn
I A
IA
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000947:Antigens, Helminth / Q000276:immunology; D017165:Ascaris suum / Q000276:immunology*; D004357:Drug Synergism; D000939:Epitopes / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008934:Mitogens / Q000494:pharmacology; D009500:Neutralization Tests; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D000939:Epitopes; D008934:Mitogens; D016753:Interleukin-10; D015847:Interleukin-4; D010047:Ovalbumin